Myogen proposes to develop and optimize a long-term culture system for adult human cardiac myocytes. Failing explanted and non-failing organ donor human hearts will be used to isolate cardiac myocytes for culture. The cultured cells will be characterized to validate their phenotype. The developed culture systems will ultimately be used to establish high throughput screening programs for identification of important molecular events in myocardial failure and remodeling and to search for compounds for the treatment of heart failure. Such a system is not currently available, and should significantly impact the search for novel treatment of heart failure, which is currently implicated in 260,000 deaths per year in the U.S. In Phase I Myogen will isolate human adult cardiac myocytes and will apply novel culture techniques to achieve survival of cells in culture for at least one month. Cultured cells will be characterized with respect to their morphology and gene expression patterns. In Phase II Myogen will use the developed culture system to demonstrate high throughput biological screens for target identification and validation and high throughput compound screens for drug research and development. In Phase III Myogen will commercialize the developed technology through compound development, collaborative research, and licensing. PROPOSED COMMERCIAL APPLICATIONS: Development of target identification and target validation for heart failure is the goal of this project. Development of high throughput screening programs for therapeutic and diagnostic identification in heart failure. It is estimated that for each validated target, approximately $30- 40 million in precommercial payments will be generated from licensing fees, R&D funding, milestone payments, and equity. This figure does not include future royalties from commercialization which will generate additional revenue.